Proinflammatory cytokine levels in the serum and cerebrospinal fluid of tuberculous meningitis patients

Abstract

The pathophysiology underlying tuberculous meningitis (TBM), the most prominent extra pulmonary tuberculosis and a serious public health problem in developing countries is still unclear. Whereas, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) are cytokines involved in cell-mediated immune response. TNF-α and IFN-γ production has earlier been shown to be associated with tissue necrosis. To see whether these cytokines have any role to play in the pathophysiology of TBM, we measured the levels of serum and cerebrospinal fluid (CSF) TNF-α and IFN-γ in 31 consecutive patients of TBM by ELISA. There was a remarkable rise (P < 0.001) in the levels of serum and CSF TNF-α and IFN-γ levels in TBM patients with respect to 20 age and sex-matched control subjects. Furthermore, TNF-α and IFN-γ levels showed a positive correlation with the severity of the disease at the end of 6 months of antibiotic therapy. Elevated TNF-α and IFN-γ levels, especially in CSF, despite of these patients undergoing multidrug therapy suggests the persistence of central nervous system inflammation. We also found an associated rise (P < 0.001) in the nitric oxide (NO) levels of serum and CSF but there was no correlation between NO levels and the severity of TBM. The continuous release of cytokines despite these patients undergoing anti-tubercular therapy suggests that TBM severity may result mainly from the immune response rather than the organism itself.